1. Radiotherapy Increases 12-LOX and CCL5 Levels in Esophageal Cancer Cells and Promotes Cancer Metastasis via THP-1-Derived Macrophages
- Author
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Mi S, Qu Y, Chen X, Wen Z, Chen P, and Cheng Y
- Subjects
radiotherapy ,12-lox ,ccl5 ,macrophage ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Si Mi, Yan Qu, Xue Chen, Zhihua Wen, Pengxiang Chen, Yufeng Cheng Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Yufeng Cheng Email shandong_sdu2019@126.comBackground: Dioxygenase 12-lipoxygenase (12-LOX) plays an important role in tumorigenesis and promotes angiogenesis and proliferation in several tumors, including prostate and breast tumors. Radiotherapy enhances the expression of 12-LOX in esophageal squamous cell carcinoma (ESCC). Two types of macrophages can be found in the tumor microenvironment. The M2 subtype accelerates tumor progression; however, the relationship between 12-LOX and macrophages is not well established. Here, we explore this interaction and its effect on ESCC to induce tumor progression.Methods and Results: RT-qPCR and Western blot analyses were used to evaluate the mRNA and protein expression levels of 12-LOX and chemokine (C-C motif) ligand 5 (CCL5) in ESCC after radiotherapy. CCL5 expression was increased by 12-LOX upregulation but was suppressed by the well-established 12-LOX inhibitor, baicalein. Furthermore, CCL5 attracted and repolarized human myeloid leukemia mononuclear cells (THP-1)-derived macrophages. Finally, ESCC co-culture with THP-1-derived macrophages led to a strong cancer migratory capacity.Conclusion: Radiation-induced 12-LOX overexpression in ESCC upregulates CCL5 expression, thereby attracting THP-1-derived macrophages and promoting their polarization to the M2 subtype, which enhances cellular metastasis.Keywords: radiotherapy, 12-LOX, CCL5, macrophage
- Published
- 2020